Ophthalmic compositions containing a synergistic combination of two polymers

ABSTRACT

Ophthalmic compositions suitable for use as artificial tears or as vehicles for ophthalmic drugs are disclosed. The compositions contain a combination of two polymers that have a synergistic effect on viscosity.

[0001] This application claims priority to U.S. Provisional Application,U.S. Ser. No. 60/478,253, filed Jun. 13, 2003.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to pharmaceutical compositions. Inparticular, this invention relates to topically administrable ophthalmiccompositions that contain certain combinations of two polymericcomponents.

[0004] 2. Description of Related Art

[0005] The use of polymeric ingredients in topically administrableophthalmic compositions is well known. Polymeric ingredients aretypically used in suspension compositions as physical stability aids,helping to keep the insoluble ingredients suspended or easilyredispersible. In solution compositions, polymeric ingredients aretypically used to increase the composition's viscosity.

[0006] Many polymers have been used in topically administrableophthalmic compositions. Included among these are cellulosic polymers,such as hydroxypropyl methylcellulose, hydroxyethyl cellulose, andethylhydroxyethyl cellulose. Also included are synthetic polymers, suchas carboxyvinyl polymers and polyvinyl alcohol. Still others includepolysaccharides such as xanthan gum, guar gum, and dextran.

[0007] Combinations of polymers have also been used in ophthalmiccompositions. Certain combinations of polymers are known to providesynergistic effects on viscosity and, in some cases, even a phasetransition from a liquid to a gel. For example, U.S. Pat. No. 4,136,173discloses ophthalmic compositions containing a combination of xanthangum and locust bean gum.

[0008] One approach to achieving a target viscosity in a topicallyadministrable ophthalmic composition might involve simply adding asufficient amount of one polymeric ingredient. Often, however, it isdesirable to minimize the total amount of polymeric additives intopically administrable ophthalmic compositions. A mixed polymer systemcontaining more than one polymer can significantly enhance the viscosityand lubrication property of a composition while minimizing total polymerconcentration and cost of materials.

SUMMARY OF THE INVENTION

[0009] The present invention is directed toward aqueous ophthalmiccompositions suitable for topical ophthalmic administration thatcomprise a viscosity enhancing amount of a polymeric ingredient whereinthe polymeric ingredient consists of a certain combination of twopolymeric ingredients. The ophthalmic compositions comprise acombination of polymeric ingredients selected from the group consistingof: hydroxypropyl methylcellulose and guar gum; hydroxypropylmethylcellulose and a carboxyvinyl polymer; carboxyvinyl polymer andguar gum; hydroxypropyl methylcellulose and hydroxyethylcellulose;hyaluronic acid and hydroxypropyl methylcellulose; and hyaluronic acidand guar gum. The compositions containing one of these selectcombinations of polymeric ingredients are useful as artificial tearproducts, and can also serve as vehicles for delivering ophthalmicdrugs.

[0010] The present invention is based upon the finding that these selectcombinations of two polymers have a synergistic effect on viscosity.

DETAILED DESCRIPTION OF THE INVENTION

[0011] Unless otherwise indicated, all ingredient concentrations arelisted as a weight/volume percentage basis (% w/v).

[0012] The ophthalmic compositions of the present invention are aqueouscompositions that include a select combination of two polymericingredients. The combination is one of the following: hydroxypropylmethylcellulose and guar gum; hydroxypropyl methylcellulose and acarboxyvinyl polymer; a carboxyvinyl polymer and guar gum; hydroxypropylmethylcellulose and hydroxyethylcellulose; hyaluronic acid andhydroxypropyl methylcellulose; and hyaluronic acid and guar gum. Allfive types of individual polymers are known and have been used inophthalmic compositions. All five types of polymers are alsocommercially available.

[0013] HPMC is commercially available from the Dow Chemical Companyunder the brand name Methocel®. HPMC is available in a variety ofgrades. Most preferred for use in the compositions of the presentinvention is Methocel E4M, (HPMC 2910), which has a number averagemolecular weight of approximately 86,000 dalton. The concentration ofHPMC in the compositions of the present invention will generally rangefrom 0.05-0.5%, and will preferably be 0.3%.

[0014] The guar gum ingredient can be guar gum or a guar gum derivative,such as the hydroxypropyl or hydroxypropyltrimonium chloride derivativesof guar gum. Guar and its derivatives are described in U.S. Pat. No.6,316,506, the entire contents of which are hereby incorporated byreference. For purposes of the present application, “guar gum” includesunsubstituted guar gum and its substituted derivatives. Guar gum andmany of its derivatives are commercially available from Rhone-Poulenc(Cranbury, N.J.), Hercules, Inc. (Wilmington, Del.) and TIC Gum, Inc.(Belcamp, Md.). A preferred derivative for use in the compositions ofthe present invention is hydroxypropyl guar (“HP-Guar”). Theconcentration of guar in the compositions of the present invention willgenerally range from 0.01-0.2%, and will preferably be 0.1%.

[0015] Carboxyvinyl polymers suitable for use in the present inventionare also known as “carbomers” or carboxypolymethylene. They arecommercially available from sources such as Noveon, Inc. (Cleveland,Ohio), which distributes them under the trade name Carbopol®. Carbopolpolymers are crosslinked, acrylic acid-based polymers. They arecrosslinked with allyl sucrose or allylpentaerythritol. Carbopolcopolymers are polymers of acrylic acid, modified by C₁₀₋₃₀ alkylacrylates, and crosslinked with allylpentaerythritol. A preferredcarboxyvinyl polymer for use in the compositions of the presentinvention is a polymer of acrylic acid crosslinked with allyl sucrose orallylpentaerythritol, which is commercially available as Carbopol® 974P.The concentration of carbomer in the compositions of the presentinvention will generally range from 0.01-0.2%, and will preferably be0.1%.

[0016] HEC is commercially available from Hercules Inc. (AqualonDivision) in a variety of grades, including Natrasol 250 LR, Natrasol250 MR and Natrasol 250 HR. A preferred HEC for use in the compositionsof the present invention is the NF grade material, which is commerciallyavailable as Natrasol 250HR. The concentration of HEC in thecompositions of the present invention will generally range from0.05-0.5%, and will preferably range from 0.1-0.2%.

[0017] Hyaluronic acid is commercially available from a variety ofsources, including Genzyme and Hyaluron Inc. Hyaluronic acid isavailable in many grades, with molecular weights ranging from 100,000 togreater than 3 million dalton.

[0018] The aqueous compositions of the present invention contain one ofthe specified combinations of polymers in a total polymer concentrationrange of 0.05-3.0%, preferably 0.2-2.0%.

[0019] In addition to the required combination of two polymericingredients, the aqueous compositions of the present invention maycontain other ingredients as excipients. For example, the compositionsmay include one or more pharmaceutically acceptable buffering agents,preservatives (including preservative adjuncts), non-ionictonicity-adjusting agents, surfactants, solubilizing agents, stabilizingagents, comfort-enhancing agents, emollients, pH-adjusting agents and/orlubricants. Preferably, the aqueous composition does not contain anypolymeric ingredients, other than the synergistic combination of the twopolymeric ingredients specified above, with the exception of polymericpreservatives for compositions that contain a preservative. If thecompositions contain a carbomer as one of the two polymers, then thecompositions of the present invention do not contain any ionictonicity-adjusting agent, such as sodium chloride, or other ionicexcipients, such as boric acid, as these ingredients have a significant,detrimental effect on the composition's viscosity.

[0020] The compositions of the invention have a pH in the range of 5-9,preferably 6.5-7.5, and most preferably 6.9-7.4. If the compositionscontain a carbomer as one of the three polymers, it is critical that thecompositions are formulated so that the target pH is not exceeded. Oncea target pH has been exceeded in compositions containing a carbomer,adding an acid such as hydrochloric acid to adjust the pH downward cancompromise the synergistic viscosity. Even relatively small amounts ofacid or salts, on the order of 0.005%, can have a significant effect onthe viscosity of compositions containing a carbomer.

[0021] The compositions of the present invention generally have anosmolality in the range of 220-320 mOsm/kg, and preferably have anosmolality in the range of 235-260mOsm/kg.

[0022] The aqueous compositions of the present invention are suitablefor use as artificial tear products to relieve symptoms of dry eye.Alternatively, the compositions of the present invention may act as avehicle for an ophthalmic drug. The compositions of the presentinvention may also be used as irrigating solutions for ophthalmic orother surgical procedures. Ophthalmic drugs suitable for use in thecompositions of the present invention include, but are not limited to:anti-glaucoma agents, such as beta-blockers including timolol,betaxolol, levobetaxolol, carteolol, miotics including pilocarpine,carbonic anhydrase inhibitors, prostaglandins, seretonergics,muscarinics, dopaminergic agonists, adrenergic agonists includingapraclonidine and brimonidine; anti-angiogenesis agents; anti-infectiveagents including quinolones such as ciprofloxacin, and aminoglycosidessuch as tobramycin and gentamicin; non-steroidal and steroidalanti-inflammatory agents, such as suprofen, diclofenac, ketorolac,rimexolone and tetrahydrocortisol; growth factors, such as EGF;immunosuppressant agents; and anti-allergic agents includingolopatadine. The ophthalmic drug may be present in the form of apharmaceutically acceptable salt, such as timolol maleate, brimonidinetartrate or sodium diclofenac. Compositions of the present invention mayalso include combinations of ophthalmic drugs, such as combinations of(i) a beta-blocker selected from the group consisting of betaxolol andtimolol, and (ii) a prostaglandin selected from the group consisting oflatanoprost; 1 5-keto latanoprost; travoprost; and unoprostoneisopropyl.

[0023] Although the amount of drug included in the compositions of thepresent invention will be whatever amount is therapeutically effectiveand will depend upon a number of factors, including the identity andpotency of the chosen drug, the total concentration of drug willgenerally be about 5% or less.

[0024] The compositions of the present invention are preferably notformulated as solutions that gel upon administration to the eye. Thecompositions illustrated in the Examples below do not gel uponadministration to the eye.

[0025] The following examples are presented to illustrate furthervarious aspects of the present invention, but are not intended to limitthe scope of the invention in any respect.

EXAMPLES Example 1 Artificial Tear Composition

[0026] A representative formulation for an artificial tear productaccording to the present invention is shown in Table 1. TABLE 1Ingredients Concentration (% w/v) Carbopol 974P 0.1 HP-Guar 0.1 Mannitol4.0 NaOH/HCl Qs to pH 7.0 Purified water Qs to 100

[0027] The composition shown in Table 1 can be prepared by at least twomethods. One method involves adding the following ingredients slowly andin the following order to heated purified water (70-80° C.)(approximately 80% of the desired batch volume) with mixing: mannitol,Carbopol 974P, and HP-Guar (waiting until each ingredient is mixed wellbefore adding the next). pH is then adjusted with 1N NaOH, and theremaining amount of purified water is added. The composition is thenautoclaved at 121° C. for thirty minutes and subsequently cooled to roomtemperature with constant stirring.

[0028] An alternative method of preparing the composition shown in Table1 is as follows. In a first container, add heated purified water (70-80°C.) (approximately 60% of the desired batch volume), then mix inmannitol, and then Carbopol 974P, waiting until each ingredient is mixedwell before adding the next. Autoclave the resulting composition at 121°C. for thirty minutes, then allow the composition to cool to roomtemperature with constant stirring (“the Carbopol composition”). In aseparate container, add purified water (approximately 30% of the desiredbatch volume), then mix in HP-Guar. Adjust the pH of the HP-Guarcomposition with 1N NaOH to pH 9. Autoclave the HP-Guar composition at121° C. for thirty minutes, then allow it to cool to room temperaturewith constant stirring (“the HP-Guar composition”), then asepticallycombine the HP-Guar composition with the Carbopol composition, andaseptically adjust the final pH to 7.0, if necessary, with 1N NaOH.

Example 2 Synergistic Effect on Viscosity (HPMC+Guar; HPMC+Carbomer;Carbomer+Guar)

[0029] The compositions shown in Table 2 were prepared and theirviscosity was determined using a Brookfield cone/plate viscometer withnumber 42 cone/plate set (30 rpm, at 25° C.) for less viscous samples(viscosity less than 20 cps) and number 52 cone/plate set (3 rpm, at 25°C.) for more viscous samples (viscosity more than 20 cps). Two peopleindependently prepared the indicated samples and measured theirviscosity values (n=1) for each person. The averages of each set ofresults are shown in Table 2. TABLE 2 Composition (% w/v) Ingredient 1 23 4 5 6 7 Mannitol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 HPMC 2910 — 0.3 — — 0.30.3 — Carbopol 974P — — 0.1 — 0.1 — 0.1 HP-Guar — — — 0.1 — 0.1 0.1NaOH/HCl q.s. q.s. q.s. q.s. q.s. q.s. q.s. pH pH pH pH pH pH pH 7.0 7.07.0 7.0 7.0 7.0 7.0 Purified Water q.s. q.s. q.s. q.s. q.s. q.s. q.s.100 100 100 100 100 100 100 Viscosity (cps) 1.1 8.2 488.1 5.3 1339.532.3 1273.0 Subst. Synergy^(@) — — — — Yes Yes Yes

Example 3 Synergistic Effect on Viscosity (HPMC+HEC)

[0030] The compositions shown in Table 3 were prepared and theirviscosity determined using a Brookfield cone/plate viscometer withnumber 42 cone/plate set (30 rpm, at 25° C.) for less viscous samples(viscosity less than 20 cps) and number 52 cone/plate set (3 rpm, at 25°C.) for more viscous samples (viscosity more than 20 cps). The HEC usedin this experiment was Natrasol 250HR as shown in the following Table.Two people independently prepared the indicated samples and measuredtheir viscosity values (n=1) for each person. The averages of each setof results are shown in Table 3. TABLE 3 Composition (% w/v) Ingredient8 9 10 11 12 13 14 15 Mannitol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 HPMC 2910— 0.3 — — — 0.3 — — HP-Guar — — 0.1 — — — 0.1 — Carbopol — — — 0.1 — — —0.1 974P Natrasol — — — — 0.1 0.1 0.1 0.1 250HR NaOH/HCl q.s. q.s. q.s.q.s. q.s. q.s. q.s. q.s. pH pH pH pH pH pH pH pH 7.0 7.0 7.0 7.0 7.0 7.07.0 7.0 Purified q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. Water 100 100100 100 100 100 100 100 Viscosity 1.0 8.0 5.2 465.9 3.0 27.7 10.9 642.0(cps) Subst. — — — — — Yes No No Synergy^(@)

Example 4 Lack of Synergistic Effect on Viscosity (PolyvinylAlcohol+Chondroitin Sulfate; Polyvinyl Alcohol+Polyvinylpyrrolidone;Chondroitin Sulfate+Polyvinylpyrrolidone)

[0031] The compositions shown in Table 4 were prepared and theirviscosity determined using a Brookfield cone/plate viscometer withnumber 42 cone/plate set (30 rpm, at 25° C.) for less viscous samples(viscosity less than 20 cps) and number 52 cone/plate set (3 rpm, at 25°C.) for more viscous samples (viscosity more than 20 cps). Two peopleindependently prepared the indicated samples and measured theirviscosity values (n=1) for each person. The averages of each set ofresults are shown in Table 4. Airvol 523S is a commercially availablepolyvinyl alcohol polymer. Chondroitin sulfate is a commerciallyavailable polymer. PVP K90 is a commercially available polyvinylpyrrolidone polymer. TABLE 4 Composition (% w/v) Ingredient 16 17 18 1920 21 22 Mannitol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 PVA (Airvol 523S) — 0.2 —— 0.2 0.2 — Chondroitin Sulfate — — 0.2 — 0.2 — 0.2 PVP (K90) — — — 0.2— 0.2 0.2 NaOH/HCl q.s. q.s. q.s. q.s. q.s. q.s. q.s. pH pH pH pH pH pHpH 7.0 7.0 7.0 7.0 7.0 7.0 7.0 Purified Water q.s. q.s. q.s. q.s. q.s.q.s. q.s. 100 100 100 100 100 100 100 Viscosity (cps) 1.0 1.5 1.3 1.41.7 1.9 1.8 Subst. Synergy^(@) — — — — No No No

Example 5 Lack of Synergistic Effect on Viscosity (PolyvinylAlcohol+Carbomer; Chondroitin Sulfate+Carbomer; Polyvinylpyrrolidone+Carbomer)

[0032] The compositions shown in Table 5 were prepared and theirviscosity determined using a Brookfield cone/plate viscometer withnumber 42 cone/plate set (30 rpm, at 25° C.) for less viscous samples(viscosity less than 20 cps) and number 52 cone/plate set (3 rpm, at 25°C.) for more viscous samples (viscosity more than 20 cps). Two peopleindependently prepared the indicated samples and measured theirviscosity values (n=1) for each person. The averages of each set ofresults are shown in Table 5. Airvol 523S is a commercially availablepolyvinyl alcohol polymer. Chondroitin sulfate is a commerciallyavailable polymer. K90 is a commercially available polyvinylpyrrolidonepolymer. TABLE 5 Composition (% w/v) Ingredient 17 18 19 23 24 25 26Mannitol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 PVA 0.2 — — — 0.2 — — (Airvol 523S)Chondroitin — 0.2 — — — 0.2 — Sulfate PVP — — 0.2 — — — 0.2 (K90)Carbopol — — — 0.1 0.1 0.1 0.1 974P NaOH/HCl q.s. pH q.s. pH q.s. pHq.s. q.s. q.s. q.s. 7.0 7.0 7.0 pH pH pH pH 7.0 7.0 7.0 7.0 PurifiedWater q.s. q.s. q.s. q.s. q.s. q.s. q.s. 100 100 100 100 100 100 100Viscosity (cps) 1.5 1.3 1.4 441.6 323.8 12.7 N/A* Subst. — — — — No NoNo Synergy^(@)

Example 6 Lack of Synergistic Effect on Viscosity (HPMC+Dextran;Guar+Dextran; Carbomer+Dextran)

[0033] The compositions shown in Table 6 were prepared and theirviscosity determined using a Brookfield cone/plate viscometer withnumber 42 cone/plate set (30 rpm, at 25° C.) for less viscous samples(viscosity less than 20 cps) and number 52 cone/plate set (3 rpm, at 25°C.) for more viscous samples (viscosity more than 20 cps). Two peopleindependently prepared the indicated samples and measured theirviscosity values (n=1) for each person. The averages of each set ofresults are shown in Table 6. TABLE 6 Composition (% w/v) Ingredient 2728 29 30 31 32 33 34 Mannitol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 HPMC 2910— 0.3 — — — 0.3 — — HP-Guar — — 0.1 — — — 0.1 — Carbopol — — — 0.1 — — —0.1 974P Dextran 70 — — — — 0.1 0.1 0.1 0.1 NaOH/HCl q.s. q.s. q.s. q.s.q.s. q.s. q.s. q.s. pH 7.0 pH pH pH pH pH pH pH 7.0 7.0 7.0 7.0 7.0 7.07.0 Purified q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. Water 100 100 100100 100 100 100 100 Viscosity 1.1 7.9 5.2 461.6 1.4 8.4 5.2 379.3 (cps)Subst. — — — — — No No No Synergy^(@)

Example 7 Effect of Salt on Viscosity for a Polymer Combination thatContains Carbomer

[0034] The compositions shown below in Table 7 were prepared todetermine the effect of the addition of salt (NaCl) on viscosity. Theviscosity of each sample was determined using a Brookfield cone/plateviscometer (52 cone, 3 rpm). The results are shown in Table 7. TABLE 7Composition (% w/v) INGREDIENT 35 36 37 38 39 Mannitol 4.0 4.0 4.0 4.04.0 HPMC 2910 0.3 0.3 0.3 0.3 0.3 Carbopol 974P 0.1 0.1 0.1 0.1 0.1 NaCl0 0.001 0.005 0.01 0.05 NaOH/HCl q.s. pH 7.0 q.s. pH 7.0 q.s. pH 7.0q.s. pH 7.0 q.s. pH 7.0 Purified Water q.s. 100 q.s. 100 q.s. 100 q.s.100 q.s. 100 Viscosity (cps) 737 430 359 212 49

Example 8 Effect of Boric Acid on Viscosity for a Polymer Combinationthat Contains Carbomer

[0035] The compositions shown below in Table 8 were prepared todetermine the effect of the addition of boric acid on viscosity. Theviscosity of each sample was determined using a Brookfield cone/plateviscometer (52 cone, 3 rpm). The results are shown in Table 8. TABLE 8Composition (% w/v) INGREDIENT 40 41 42 43 44 Mannitol 4.0 4.0 4.0 4.04.0 HPMC 2910 0.3 0.3 0.3 0.3 0.3 Carbopol 974P 0.1 0.1 0.1 0.1 0.1Boric acid 0 0.001 0.005 0.01 0.05 NaOH/HCl q.s. pH 7.0 q.s. pH 7.0 q.s.pH 7.0 q.s. pH 7.0 q.s. pH 7.0 Purified Water q.s. 100 q.s. 100 q.s. 100q.s. 100 q.s. 100 Viscosity (cps) 657 534 362 233 65

[0036] The invention has been described by reference to certainpreferred embodiments; however, it should be understood that it may beembodied in other specific forms or variations thereof without departingfrom its spirit or essential characteristics. The embodiments describedabove are therefore considered to be illustrative in all respects andnot restrictive, the scope of the invention being indicated by theappended claims rather than by the foregoing description.

What is claimed is:
 1. An aqueous composition suitable for topicalophthalmic administration comprising a viscosity enhancing amount ofcombination of two polymers having a synergistic effect on thecomposition's viscosity and wherein the combination of two polymers isselected from the group consisting of hydroxypropyl methylcellulose andguar gum; hydroxypropyl methylcellulose and a carboxyvinyl polymer; acarboxyvinyl polymer and guar gum; hydroxypropyl methylcellulose andhydroxyethylcellulose; hyaluronic acid and hydroxypropylmethylcellulose; and hyaluronic acid and guar gum, provided that if thecomposition comprises a carboxyvinyl polymer then the composition doesnot contain sodium chloride or boric acid.
 2. The composition of claim 1wherein the combination of two polymers is a combination of ahydroxypropyl methylcellulose and guar gum.
 3. The composition of claim1 wherein the combination of two polymers is a combination ofhydroxypropyl methylcellulose and a carboxyvinyl polymer.
 4. Thecomposition of claim 1 wherein the combination of two polymers is acombination of a carboxyvinyl polymer and guar gum.
 5. The compositionof claim 1 wherein the combination of two polymers is a combination ofhydroxypropyl methylcellulose and hydroxyethylcellulose.
 6. Thecomposition of claim 1 wherein the combination of two polymers is acombination of hyaluronic acid and hydroxypropyl methylcellulose.
 7. Thecomposition of claim 1 wherein the combination of two polymers is acombination of hyaluronic acid and guar gum.
 8. The composition of claim1 wherein the carboxyvinyl polymer is a polymer of acrylic acidcrosslinked with allyl sucrose or allylpentaerythritol, thehydroxypropyl methylcellulose has a number average molecular weight ofapproximately 86,000 dalton, the guar gum is hydroxypropyl guar.
 9. Thecomposition of claim 1 wherein the total concentration of the twopolymers ranges from 0.05-3.0% (w/w).
 10. The composition of claim 9wherein the total concentration of the two polymers ranges from 0.2-2.0%(w/w).
 11. The composition of claim 1 further comprising an ingredientselected from the group consisting of pharmaceutically acceptablebuffering agents; preservatives; non-ionic tonicity-adjusting agents;surfactants; solubilizing agents; stabilizing agents; comfort-enhancingagents; emollients; pH-adjusting agents; and lubricants.
 12. Thecomposition of claim 1 further comprising an ophthalmic drug.
 13. Thecomposition of claim 12 wherein the ophthalmic drug is selected from thegroup consisting of anti-glaucoma agents; anti-angiogenesis agents;anti-infective agents; non-steroidal and steroidal anti-inflammatoryagents; growth factors; immunosuppressant agents; and anti-allergicagents.
 14. A method of alleviating the symptoms of dry eye comprisingtopically administering to the eye an aqueous composition comprising aviscosity enhancing amount of a combination of two polymers having asynergistic effect on the composition's viscosity and wherein thecombination of two polymers is selected from the group consisting ofhydroxypropyl methylcellulose and guar gum; hydroxypropylmethylcellulose and a carboxyvinyl polymer; a carboxyvinyl polymer andguar gum; hydroxypropyl methylcellulose and hydroxyethylcellulose;hyaluronic acid and hydroxypropyl methylcellulose; and hyaluronic acidand guar gum, provided that if the composition comprises a carboxyvinylpolymer then the composition does not contain sodium chloride or boricacid.